We collected mercury observations as part of the Nitrogen, Oxidants, Mercury, and Aerosol Distributions, Sources, and Sinks (NOMADSS) aircraft campaign over the southeastern US between 1 June and ...15 July 2013. We use the GEOS-Chem chemical transport model to interpret these observations and place new constraints on bromine radical initiated mercury oxidation chemistry in the free troposphere. We find that the model reproduces the observed mean concentration of total atmospheric mercury (THg) (observations: 1.49 ± 0.16 ng m−3, model: 1.51 ± 0.08 ng m−3), as well as the vertical profile of THg. The majority (65 %) of observations of oxidized mercury (Hg(II)) were below the instrument's detection limit (detection limit per flight: 58–228 pg m−3), consistent with model-calculated Hg(II) concentrations of 0–196 pg m−3. However, for observations above the detection limit we find that modeled Hg(II) concentrations are a factor of 3 too low (observations: 212 ± 112 pg m−3, model: 67 ± 44 pg m−3). The highest Hg(II) concentrations, 300–680 pg m−3, were observed in dry (RH < 35 %) and clean air masses during two flights over Texas at 5–7 km altitude and off the North Carolina coast at 1–3 km. The GEOS-Chem model, back trajectories and observed chemical tracers for these air masses indicate subsidence and transport from the upper and middle troposphere of the subtropical anticyclones, where fast oxidation of elemental mercury (Hg(0)) to Hg(II) and lack of Hg(II) removal lead to efficient accumulation of Hg(II). We hypothesize that the most likely explanation for the model bias is a systematic underestimate of the Hg(0) + Br reaction rate. We find that sensitivity simulations with tripled bromine radical concentrations or a faster oxidation rate constant for Hg(0) + Br, result in 1.5–2 times higher modeled Hg(II) concentrations and improved agreement with the observations. The modeled tropospheric lifetime of Hg(0) against oxidation to Hg(II) decreases from 5 months in the base simulation to 2.8–1.2 months in our sensitivity simulations. In order to maintain the modeled global burden of THg, we need to increase the in-cloud reduction of Hg(II), thus leading to faster chemical cycling between Hg(0) and Hg(II). Observations and model results for the NOMADSS campaign suggest that the subtropical anticyclones are significant global sources of Hg(II).
Summary
Background
Erdheim–Chester disease (ECD) is a rare condition and there is limited information available regarding its cutaneous manifestations.
Objectives
To describe the clinical and ...histopathological features of cutaneous involvement in ECD.
Methods
This study is a single‐centre retrospective analysis of patients 18 years old and older with biopsy‐proven diagnosis of ECD between 1 January 1990 and 1 April 2017. Patients from this cohort were screened for cutaneous manifestations, and BRAF c.1799T>A (p.V600E) mutational analysis was conducted in novel skin manifestations. Primary outcomes included cutaneous manifestations (morphology and topography of lesions) and BRAF mutation status in novel cutaneous findings.
Results
Of 71 patients with ECD, 15 patients (21%; median age 52 years) presented with cutaneous manifestations. The most common finding was the presence of xanthelasma‐like lesions (n = 8). Two patients had nonfacial cutaneous xanthomas. Seven patients presented with nonxanthomatous cutaneous involvement, with the most common finding being subcutaneous nodules (n = 5). A single patient presented with granuloma annulare‐like lesions. Another patient with mixed ECD and Langerhans cell histiocytosis presented with lightly scaling, pink‐red macules. In three patients, the appearance of skin lesions was the first manifestation of the disease. Most patients presented with bone/extremity pain, weight loss and other constitutional symptoms at the time of diagnosis. The BRAF V600E mutation was not found in patients with panniculitis‐like and granuloma annulare‐like lesions.
Conclusions
The most common presentation in ECD is the presence of periorbital xanthelasma‐like lesions. Other presentations include nonfacial cutaneous xanthomas, panniculitis‐like lesions and granuloma annulare‐like lesions. Associated symptoms at presentation include bone/extremity pain and weight loss.
What's already known about this topic?
Erdheim–Chester disease is a rare form of non‐Langerhans cell histiocytosis characterized by lipid‐laden macrophage infiltration of tissue and subsequent fibrosis.
Cutaneous involvement is found in approximately 25% of patients, with the majority presenting with periorbital xanthelasma‐like lesions.
What does this study add?
We report two novel cutaneous findings: panniculitis‐like lesions and granuloma annulare‐like lesions.
Associated bone/extremity pain and weight loss should raise suspicion for Erdheim–Chester disease.
Linked Comment: Rose. Br J Dermatol 2020; 182:273–274.
The development of multidrug resistance (due to drug efflux by P-glycoproteins) is a major drawback with the use of paclitaxel (PTX) in the treatment of cancer. The rationale behind this study is to ...prepare PTX nanoparticles (NPs) for the reversal of multidrug resistance based on the fact that PTX loaded into NPs is not recognized by P-glycoproteins and hence is not effluxed out of the cell. Also, the intracellular penetration of the NPs could be enhanced by anchoring transferrin (Tf) on the PTX-PLGA-NPs. PTX-loaded PLGA NPs (PTX-PLGA-NPs), Pluronic®P85-coated PLGA NPs (P85-PTX-PLGA-NPs), and Tf-anchored PLGA NPs (Tf-PTX-PLGA-NPs) were prepared and evaluted for cytotoxicity and intracellular uptake using C6 rat glioma cell line. A significant increase in cytotoxicity was observed in the order of Tf-PTX-PLGA-NPs > P85-PTX-PLGA-NPs > PTX-PLGA-NPs in comparison to drug solution. In vivo biodistribution on male Sprague-Dawley rats bearing C6 glioma (subcutaneous) showed higher tumor PTX concentrations in animals administered with PTX-NPs compared to drug solution.
Abstract Background In addition to classical manifestations of Chikungunya infection, severe infections requiring hospitalization were reported during outbreaks in India in 2006. Objectives To ...describe the systemic syndromes and risk groups of severe Chikungunya infections. Study design We prospectively investigated suspected Chikungunya cases hospitalized in Ahmedabad, Gujarat during September–October 2006, and retrospectively investigated laboratory-confirmed Chikungunya cases hospitalized with neurologic syndromes in Pune, Maharashtra. Hospital records were reviewed for demographic, comorbidity, clinical and laboratory information. Sera and/or cerebrospinal fluid were screened by one or more methods, including virus-specific IgM antibodies, viral RNA and virus isolation. Results Among 90 laboratory-confirmed Chikungunya cases hospitalized in Ahmedabad, classical Chikungunya was noted in 25 cases and severe Chikungunya was noted in 65 cases, including non-neurologic (25) and neurologic (40) manifestations. Non-neurologic systemic syndromes in the 65 severe Chikungunya cases included renal (45), hepatic (23), respiratory (21), cardiac (10), and hematologic manifestations (8). Males (50) and those aged ≥60 years (50) were commonly affected with severe Chikungunya, and age ≥60 years represented a significant risk. Comorbidities were seen in 21 cases with multiple comorbidities in 7 cases. Among 18 deaths, 14 were males, 15 were aged ≥60 years and 5 had comorbidities. In Pune, 59 laboratory-confirmed Chikungunya cases with neurologic syndromes were investigated. Neurologic syndromes in 99 cases from Ahmedabad and Pune included encephalitis (57), encephalopathy (42), and myelopathy (14) or myeloneuropathy (12). Conclusions Chikungunya infection can cause systemic complications and probably deaths, especially in elderly adults.
To assess whether the risk of incidence of Alzheimer disease (AD) varies over time. The increase in numbers of people at the oldest ages in the population will bring an increase in the number of ...people with AD. Projections of the size of the increase assume the risk of AD is constant.
All persons age 65 or older in a biracial, geographically defined area were invited to participate in a home interview every 3 years. From the approximately 10,000 participants, stratified random samples were selected for detailed clinical evaluation. At each cycle, individuals determined free of AD in a previous cycle, either by examination or by high score on cognitive function tests, were sampled in the subsequent cycle for evaluation for incident AD. The evaluations for disease were structured and uniform across time. These analyses include 1,695 subjects evaluated for incident disease from 1997 through 2008.
AD developed in 360 participants. Change over time in risk of incident disease was assessed in logistic regression analyses including evaluation date and controlling for age, gender, education, race, interval from disease-free designation to evaluation for incident disease, and sample design. The time variable (in years) was not significant (odds ratio = 0.970, 95% confidence interval = 0.902 to 1.044).
The null relation of evaluation date to disease incidence suggests no recent change in risk of AD over time, and supports this assumption for projections of AD.
In present research the serrated flow has been observed successfully after a critical amount of strain. Two relationships between the critical strain and temperature i.e. normal and inverse, ...corresponding to each serration type were studied. In order to investigate systematically the onset of serrated flow and serration type in NZ31 alloy, samples in solutionized condition were tensile tested at the temperature ranging from 100°C to 300°C with the strain rate ranging from 1×10−4s−1 to 1×10−2s−1. Results showed that normal critical strain appeared with type A and B serrated flow at temperature from 150°C to 250°C, and inverse critical strain appeared with type C at temperature from 275°C to 300°C. Through analyzing the mechanism of three serration types, we found that the production of serration required improvement in diffusion for solute atoms for pinning process at low temperature, and enhance the moving ability of dislocations for unpinning process at high temperature, which need the assistance of the strain and stress respectively. So, in this work, the critical strain for pinning and the critical stress for unpinning processes were defined, which give a better explanation to the variation tendency of two definitions in accordance with temperature. Furthermore, this relationship results in the critical strain for onset of serrated flow changing from normal to inverse and corresponding different serrations.
Alzheimer’s disease (AD) is a challenging neurodegenerative condition, necessitating early diagnosis and intervention. This research leverages machine learning (ML) and graph theory metrics, derived ...from resting-state functional magnetic resonance imaging (rs-fMRI) data to predict AD. Using Southwest University Adult Lifespan Dataset (SALD, age 21–76 years) and the Open Access Series of Imaging Studies (OASIS, age 64–95 years) dataset, containing 112 participants, various ML models were developed for the purpose of AD prediction. The study identifies key features for a comprehensive understanding of brain network topology and functional connectivity in AD. Through a 5-fold cross-validation, all models demonstrate substantial predictive capabilities (accuracy in 82–92% range), with the support vector machine model standing out as the best having an accuracy of 92%. Present study suggests that top 13 regions, identified based on most important discriminating features, have lost significant connections with thalamus. The functional connection strengths were consistently declined for substantia nigra, pars reticulata, substantia nigra, pars compacta, and nucleus accumbens among AD subjects as compared to healthy adults and aging individuals. The present finding corroborate with the earlier studies, employing various neuroimagining techniques. This research signifies the translational potential of a comprehensive approach integrating ML, graph theory and rs-fMRI analysis in AD prediction, offering potential biomarker for more accurate diagnostics and early prediction of AD.
There has been a recent upsurge in the cases of Multisystem inflammatory syndrome in children (MIS-C) associated with Coronavirus disease (COVID-19). We performed a systematic review and ...meta-analysis on the demographic profile, clinical characteristics, complications, management, and prognosis of this emerging novel entity.
Using a predefined search strategy incorporating MeSH terms and keywords, all known literature databases were searched up till 10th July 2020. The review was done in accordance with PRISMA guidelines and registered in PROSPERO (CRD4202019757).
Of the 862 identified publications, 18 studies comprising 833 patients were included for meta-analysis. The socio-demographic profile showed male predilection (p = 0.0085) with no significant racial predisposition. A higher incidence of gastrointestinal symptoms (603/715, 84.3%), myocarditis (191/309, 61.8%), left ventricular dysfunction (190/422, 45.0%), pericardial (135/436, 31.0%) and neurological symptoms (138/602, 22.9%) was reported. Serological evidence of SARS-CoV-2 had higher sensitivity compared to rtPCR (291/800, 36.4% vs 495/752, 65.8%; p < 0.001). Coronary artery anomaly (CAA) was reported in 117/681 in 9 publications (17.2%). A total of 13 (1.6%) fatalities were reported.
Clinicians need to be vigilant in identifying the constellation of these symptoms in children with clinical or epidemiologic SARS-CoV-2 infection. Early diagnosis and treatment lead to a favorable outcome.
Key message This review analyses the demographic profile, clinical spectrum, management strategies, prognosis, and pathophysiology of MIS-C among children with SARS-CoV-2 infection. The stark differences of MIS-C from Kawasaki disease with respect to demographics and clinical spectrum is addressed. Over-reliance on rtPCR for diagnosis can miss the diagnosis of MIS-C. New addition to existing literature The first systematic review and meta-analysis of published literature on MIS-C associated with COVID-19.
The article will serve to spread awareness among the clinicians regarding this emerging novel entity, so that diagnosis can be made early and management can be initiated promptly.
In an experiment performed at Lawrence Berkeley National Laboratory's 88-inch cyclotron, the isotope 244Md was produced in the 209Bi (40Ar , 5n) reaction. Decay properties of 244Md were measured at ...the focal plane of the Berkeley Gas-filled Separator, and the mass number assignment of A = 244 was confirmed with the apparatus for the identification of nuclide A . The isotope 244Md is reported to have one, possibly two, α -decaying states with α energies of 8.66(2) and 8.31(2) MeV and half-lives of 0.4 + 0.4 − 0.1 and ∼ 6 s , respectively. Additionally, first evidence of the α decay of 236Bk was observed and is reported.
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